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“IT IS ALL ABOUT TRUST.

TRUST IS THE FOUNDATION OF ANTIMICROBIAL STEWARDSHIP.”

PHARMACISTS ON THE FRONT LINE

THE FIGHT AGAINST ANTIMICROBIAL RESISTANCE

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DONNING HER WHITE COAT in the halls of Williamson Medical Center in Franklin, TN, Montgomery Green, PharmD, BCPS, is embroiled in an infectious disease arms race.

As pharmacy chair of her hospital’s antimicrobial stewardship committee, Green, an associate professor of pharmacy practice at Belmont University College of Pharmacy, is on the front line of the battle against antimicrobial resistance.

Alongside her team of fellow war-riors—pharmacists, physicians, nurses, and microbiologists—Green combs through patient charts every day for signs of inappropriate antimicrobial use. “I spend roughly 25% of my time performing antimicrobial stewardship activities,” said Green. This is on top of her responsibilities as an internal medi-cine pharmacist, professor, and preceptor for residents and student pharmacists.

Green is not the only one. All over the country, pharmacists are stepping up and leading antimicrobial steward-ship efforts.

“It is extremely important [for phar-macists to be involved],” said Eric Myers, PharmD, BCPS, BCIDP, infec-tious diseases clinical pharmacy spe-cialist at Adventist Health Bakersfield in California. “The consequences of not getting antibiotic misuse under control are going to be devastating. … We really need this to be a priority.”

A GLOBAL HEALTH CRISISThe United Nations and the World Health Organization have branded antimicrobial resistance a global health emergency. CDC claims that more than 2 million people are infected with drug-resistant bacteria each year in the United States alone. And each year, at least 23,000 of them lose their lives.

According to a 2014 U.K. study, if the current trend continues, an addi-tional 10 million people worldwide will die every year from drug-resistant bacteria by 2050—more than currently die from cancer. Without effective interventions, a post-antibiotic era, where a simple cut could mean life or death, looms ahead.

In the face of this crisis, CDC has championed antimicrobial steward-ship programs (ASPs) as a crucial line

of defense, recommending in 2014 that all acute care hospitals implement ASPs. According to the agency, ASPs not only optimize antibiotic treatment and reduce associated adverse events, such as the increased risk of life-threatening Clostridioides difficile infections, but also improve patient care and safety.

Embedded in CDC’s Core Elements of Hospital ASPs is the drug expertise of a single pharmacist leader.

THE ‘THREE DS’ OF STEWARDSHIP“As pharmacists, we are the medication efficacy and safety experts,” said Kerry LaPlante, PharmD, FCCP, FIDSA, who is infectious diseases pharmacotherapy specialist, professor of pharmacy at the University of Rhode Island, and director of the Rhode Island Infectious Diseases Fellowship and Research Programs at the U.S. Department of Veterans Affairs (VA)

Medical Center in Providence, RI. “Many of us are formally trained in infectious dis-

eases and antibiotic use. We know the pharma-cokinetics; we know the pharmacodynamics; we know the drug–drug

interactions, the lab–drug interactions, the food–drug

interactions,” she said. “No one has that training or expertise like we

do, and that’s why I think pharmacists need to lead antimicrobial stewardship.”

LaPlante learned the ramifications of antimicrobial resistance and her value as a pharmacist early in her career. As an intern, she witnessed her first patient, a

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PHARMACISTS ON THE FRONT LINE

THE FIGHT AGAINST ANTIMICROBIAL RESISTANCE

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young adult with cystic fibrosis, succumb to a multidrug-resistant infection after receiving a double lung transplant.

“Even as an intern, pulmonologists were asking me what to do to optimize the antibiotics and drug levels. … I felt very needed on that team,” she said. “It was a really sad ending for the patient. … I remember that to this day.”

Now, LaPlante spearheads steward-ship efforts and directs an antimicro-bial stewardship fellowship training program—the first in the VA health sys-tem and the second nationally—at the Providence VA. With her team, she pro-vides prospective audit and feedback by reviewing antibiotic prescriptions and therapies for the “three Ds” of traditional

stewardship—drug, dose, and duration.Green also leads daily prospective

reviews in her ASP. Using a clinical deci-sion support system, she screens for pos-itive urine or blood cultures, C. difficile infections, duplicate therapies, and anti-biotic treatments longer than 72 hours. She also assesses high-risk or broad-spectrum antibiotics and keeps an eye out for asymptomatic patients receiving antibiotic treatment.

When antibiotic misuse is flagged during the review process, Green com-municates her recommendations to the prescribers either in person or over the

phone. “We have a multidisciplinary rounding meeting every day with our hospitalist physicians, and that’s where we make most of our interventions,” said Green. “Our acceptance rate tends to be about 90% of our recommendations.”

In this sense, pharmacists act as gate-keepers, said Navaneeth Narayanan, PharmD, MPH, BCPS, infectious diseases pharmacist, and cochair and pharmacist director of Robert Wood Johnson Univer-sity Hospital’s stewardship committee in New Brunswick, NJ.

One of two core components of Nara-yanan’s ASP is an antimicrobial restric-tion policy, under which prescriptions for “restricted antibiotics”—those that have high costs, high safety risks, or are

reserved for more aggressive, multidrug-resistant organisms—are thoroughly reviewed and require consultation from the infectious diseases consult service.

The second core component involves rapid diagnostics. “We have a fantastic relationship with the microbiology lab-oratory,” he said. With the help of con-temporary rapid diagnostic technology in the lab, Narayanan and his team of infectious diseases attending physicians are able to get results from blood cul-tures faster, which allows them to appro-priately prescribe the right antibiotic for the infection at hand.

A MULTIDISCIPLINARY EFFORTGreen attributes the high acceptance rate and success of her program, which was recognized by PEW Charitable Trusts, to its collaborative, multidisciplinary team. The antimicrobial stewardship adminis-trative committee consists of representa-tives from the hospital’s different service lines, including Green, the primary phy-sician, hospitalists, intensivists, critical care and emergency department phar-macists, the clinical pharmacy manager, the chief nursing officer, the clinical informatics manager, the laboratory ser-vice director, and the director of patient safety and quality control.

Together, they meet once a month to discuss stewardship initiatives and inter-ventions on a hospitalwide scale.

“It’s really helpful for us to sit around a table and have people from so many dif-ferent perspectives when we are starting a new initiative,” said Green. It is espe-cially useful when thinking of potential pitfalls and how different patient popu-lations will be affected, she said.

Green recounted a time before the creation of the multidisciplinary com-mittee when her team had neglected to consider an entire patient subset while working on a stewardship proj-ect. “It wasn’t until someone [from that department] brought it up that we real-ized [our oversight],” she said. “We real-ized then that, if we’re going to grow the program, if we are going to really impact our hospital system as a whole, we need [everyone involved].”

LaPlante, who also works with a mul-tidisciplinary team of pharmacists, phy-sicians, nurses, infection preventionists, microbiologists, nurse practitioners, and physician assistants, agrees. “If we’re going to implement a new order set or policy, I wouldn’t dare do it without buy-in,” she said. “[When we roll out those initiatives], we all own it. It’s not mine or pharmacy’s by any means—it’s ours.”

Getting input and buy-in from fel-low providers before implementing any intervention is now a huge focus for Green’s committee. “It’s vital—with-out a doubt,” she said. “Having support from such a diverse committee really has made it much easier for a lot of our initiatives to not only happen but hap-pen more quickly.”

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Left to right: Kelly Byrge, MD, infectious diseases physician, and Montgomery Williams Green, PharmD, discuss antibiotic regimens for patients.

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‘HANDSHAKE STEWARDSHIP’It all goes back to building and foster-ing relationships, said LaPlante. “It is all about trust. Trust is the foundation of antimicrobial stewardship. If your providers don’t trust you, they’re not going to take your recommendation.”

Hesitant providers can often be a challenge for pharmacists practicing in new ASPs. “It’s an issue with pri-oritization,” said Myers, who found engaging physicians to be one of his biggest initial barriers. “This is some-thing that’s a huge priority for me, but it’s not a huge priority for them.”

“[But] effective stewardship is a marathon, not a sprint,” said Myers. Building those bridges takes time and effort, and it often means having physicians’ backs and starting with smaller recommendations. It also means practicing what LaPlante calls “handshake stewardship”—commu-nicating with providers face to face instead of on the phone—whenever possible.

During the nascence of her pro-gram, LaPlante would hold monthly antimicrobial stewardship commit-tee meetings, inviting the chief of surgery, chief of pulmonology, and other providers from whom she needed support. For her, the key was to make sure that they knew her on a first-name basis and to call them only for high-level interventions.

“Now, after being here 15 years, if I’m calling about an interven-tion, they’re going to listen to me because they know that when I call, it’s serious, and it’s important,” said LaPlante.

As her ASP evolved, LaPlante made sure that she and her trainees always gave the “why” behind their recom-mendations. Every intervention was an opportunity to educate and change the prescribers’ behavior to align with stewardship goals.

Over the years, she found that the pharmacists had to intervene less, which has freed up their time to focus on new pathways, policies, and order sets.

“It’s a pretty well-oiled machine. … We work well as a team, and we help each other out,” said LaPlante.

STEPPING OUT OF YOUR BUBBLEFor Myers, engaging his community is the ultimate goal. He chairs the Kern Antimicrobial Stewardship Consortium, a collaborative effort among the Kern County Department of Public Health, the California Department of Public Health, and all the hospitals in Kern County, CA, including eight acute care hospitals, four critical access hospitals, and a rehab hospital. The consortium’s innovative and collaborative approach to stewardship won the Baxter Leader-ship Excellence Awards in Pharmacy (LEAP) Gold Award in 2017.

Myers’ consortium primarily tar-geted the use of fluoroquinolones, with the goal of reducing C. difficile rates in the county. As part of the process, rep-resentatives from each branch—a mix of pharmacists, infection preventionists, and microbiologists—met quarterly to discuss best practices, along with dif-ferent challenges and solutions for their respective sites.

Over the past 2 years, their efforts cut fluoroquinolone use by more than 50% and reduced C. difficile rates by 35% countywide.

Now, Myers is moving to expand the consortium’s stewardship efforts outside of the hospitals to outpatient clinics and long-term care settings like nursing homes, where a common sce-nario involves older adults experienc-ing mental status changes that family members and providers assume result from a UTI. Antibiotic treatment is then

prescribed, often without checking for the patients’ hydration and fluid intake, possible drug interactions, environmen-tal changes, or other conditions that may have caused the status change.

“Typically, a hospital will have its own stewardship program that basi-cally exists in a bubble—they kind of do their own thing. The hospital down the street will do their own thing. They will ignore places like nursing homes and outpatient clinics,” said Myers.

“[But] antibiotic resistance is really a societal problem,” he said. “I could have the best stewardship program on the planet at my hospital, but if all the other hospitals aren’t really doing [steward-ship], and the nursing homes and pri-mary care physicians are just handing out antibiotics, then resistance rates will keep going up. C. difficile rates will keep going up.”

Green also believes strongly in the importance of collaborating and con-necting with other providers outside of her own hospital, especially fel-low pharmacists. “We don’t practice in silos,” she emphasized.

Guided by this philosophy, Green and her team started an antimicrobial stew-ardship symposium for their region, which has since expanded statewide to create a space for pharmacists and other providers to connect and network.

“[It is so important] to talk to other [providers] to figure out what they are doing, how they’ve been successful, and how they have solved problems that you may be having,” she said.

Green discusses patients with PGY-1 pharmacy residents Nate Berger, PharmD (left), and Bayar Haji, PharmD (right).

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A COMMUNITY EFFORT“We need everyone involved,” said Narayanan, who is also clinical assis-tant professor at Rutgers University Ernest Mario School of Pharmacy. “You don’t have to be residency trained or infectious diseases trained. The [phar-macists] working in the community are the ones doing the most important job because that’s where most of the anti-biotic prescriptions are going.”

Right now, the majority of antimicro-bial stewardship efforts in the United States are rooted in hospitals. However, according to CDC, an estimated 80% to 90% of antibiotics used in the United States are in the outpatient setting. Of those, 50% are prescribed inappropri-ately, including 30% that are unneces-sary.

“There’s a huge disparity there,” said Myers, “and I think pharmacists make sense as the people to address that.”

To tackle this issue, Myers said that he would like to see a bigger focus on tran-sitions of care. “We tend to focus on lim-iting duration of therapy when some-body’s in the hospital, but once they get discharged, nobody catches it, and they end up with another prescription for 10 more days of antibiotics,” he said. “A lot of times, that’s more than they even got at the hospital.”

Another big stewardship focus in the outpatient world is upper respira-tory tract infections, said LaPlante. CDC reports that at least half of the antibiotic prescriptions for acute respiratory infec-tions in the United States are unwar-ranted because 90% to 98% of these infec-tions are caused by viruses, not bacteria.

Narayanan sees this as a huge oppor-tunity for community pharmacists to step in, encouraging them to intervene if they see a prescription for an antibiotic treatment that’s inappropriate or longer than the recommended duration.

“Have a conversation with the doc,” he said. “[Explain that overtreatment] might introduce unwanted issues, like disrupting the patient’s microbiome, [increasing] the risk of C. difficile infec-tions and adverse events, and introduc-ing selective pressure leading to antibi-otic resistance.”

Beyond reaching out to prescribers, educating patients is imperative to stew-

ardship. This is where LaPlante sees community pharmacists making the big-gest impact.

But when it comes to these conversa-tions, LaPlante said it is important to be culturally aware. She refers to the vac-cine world as a model. “Our Hispanic community, for example, feels a sense of duty,” she said. “They’re not as con-cerned about themselves, but if they can protect their loved ones from getting sick, they’ll get a vaccine.”

Understanding those cultural nuances is essential when educating patients about antibiotics. “It goes back to trust again,” LaPlante said. “Understanding different communities, different mind-sets, different groups—where their trust lies. It’s not one-size-fits-all. … It’s about teaching [patients] in a way that’s mean-ingful to them. … I think that’s the way to change the behavior.”

A HOPEFUL FUTUREAs the fight against antimicrobial resis-tance becomes an increasing global pri-ority, antimicrobial stewardship is racing to the forefront of public minds.

“Forget health care media, it’s in the general media. It’s in the New York Times, it’s on CNN, it’s on international news, it’s all over the place,” said Narayanan. “Everyone is paying attention, and I think pharmacists are going to be at the center of all of it.”

LaPlante thinks this global focus is reminiscent of how people from all disci-plines—patients, providers, social work-ers, and researchers—came together dur-ing the HIV/AIDS epidemic in the 1980s.

“Now, more than ever, I’m seeing phy-sicians, pharmacists, nurses, microbiolo-gists working together to combat antibi-otic resistance,” said LaPlante. “The HIV community is a perfect model … on how health care works together. I’m starting

to see that same trend in the infectious diseases world.”

For Myers, it’s the innovative people working in the field of antimicrobial stewardship who energize him. And Green wants this innovation to keep moving forward, urging pharmacists to continue seeking ways to improve and avoid becoming stagnant.

Across the board, Green, LaPlante, Narayanan, and Myers encourage their fellow pharmacists to further their knowledge and training on steward-ship, whether in the form of certificate programs or board certification.

“Right now, there are two fantastic training programs out there for phar-macists, nurses, and physicians,” said LaPlante. “One is SIDP—Society of Infectious Diseases Pharmacists—and [the other] is MAD-ID—Making A Dif-ference in Infectious Diseases.” LaPlante is currently the president of SIDP and serves on the scientific advisory board of MAD-ID.

Green, who did the certificate program through SIDP, knows firsthand the ben-efits of continuous professional develop-ment in stewardship. “I was not formally trained as an infectious diseases phar-macist,” she said. But all it takes is a pas-sion and drive to make an impact.

This is a fun and exciting field for pharmacists because it’s always evolving, said Green. “Bacteria are always going to be smarter than us, and they’re always going to find new ways to develop resis-tance.”

This is why pharmacists will always be vital in the fight against antimicrobial resistance, and why it’s essential to edu-cate future pharmacists about steward-ship, Green said. “It really gives me hope that the specialty will continue to grow.”

Aina Abell, assistant editor

Back row, left to right: Patti Walton, MHSA, MT(ASCP); Lori Orme, RN, FACHE; Michael Wright, PharmD; Tracey Bastian, PharmD; Jeffrey Culp, MD. Front row, left to right: Cassie Davenport, RN, BSN, MBA; Montgomery Williams Green, PharmD; Kelly Byrge, MD; Jonathon Pouliot, PharmD.

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